Bryophyllum pinnatum compounds inhibit oxytocin-induced signalling pathways in human myometrial cells

Introduction Preterm birth is one of the leading causes of neonatal morbidity and mortality [1]. Bryophyllum pinnatum is an herbal medicine [2], which has been used as a well-tolerated tocolytic for many years in perinatal centres in Switzerland, mostly as add-on therapy.

Aim Our aim was to identify fractions of B. pinnatum press juice (BPJ) that contribute to its inhibitory effect on the increase of intracellular free calcium concentration ([Ca²⁺]_i) and on the activation of the MAPK cascade of the oxytocin signalling pathway.

Method Experiments were performed with human myometrial telomerase reverse transcriptase cells (hTERT-C3). [Ca²⁺]_i was measured with a fluorescent probe (Fura-2), and phosphorylation of MAPK proteins was analysed by immunoblotting. In all signalling experiments, cells were stimulated with oxytocin, in the absence or in the presence of BPJ and corresponding fractions.

Results The bufadienolide- and flavonoid-enriched fractions from BPJ led to a concentration-dependent reduction of oxytocin-induced increase of [Ca²⁺]_i, but none of them was as strong as BPJ. However, the combination of the two fractions had a synergistic effect comparable to BPJ. BPJ and bufadienolide-enriched fraction inhibited oxytocin-driven activation of MAPKs SAPK/JNK and ERK1/2. The effect of BPJ on oxytocin signalling pathway was comparable to that of the oxytocin-receptor antagonist and tocolytic agent atosiban.

Conclusion Our findings show that BPJ inhibits several oxytocin-induced signalling pathways involved in the regulation of myometrial contractility and further substantiate the use of BPJ in the treatment of preterm labour.

Publikationsverlauf

Artikel online veröffentlicht:
13. Juni 2022

• References

• 1 Romero R. et al. Science 2014; 35: 760-765
• 2 Hamburger M. et al. Natural Prod Commun 2017; 12: 1359-1364